title: Double dissociation in the anatomy of socioemotional disinhibition and executive functioning in dementia.
abstract: OBJECTIVE
  To determine whether socioemotional disinhibition and executive dysfunction are related to dissociable patterns of brain atrophy in neurodegenerative disease. Previous studies have indicated that behavioral and cognitive dysfunction in neurodegenerative disease are linked to atrophy in different parts of the frontal lobes, but these prior studies did not establish that these relationships were specific, which would best be demonstrated by a double dissociation.
  
  
  METHODS
  Subjects included 157 patients with neurodegenerative disease. A semiautomated parcellation program (Freesurfer) was used to generate regional cortical volumes from structural MRI scans. Regions of interest (ROIs) included anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Socioemotional disinhibition was measured using the Neuropsychiatric Inventory. Principal component analysis including 3 tasks of executive function (EF; verbal fluency, Stroop Interference, modified Trails) was used to generate a single-factor score to represent EF.
  
  
  RESULTS
  Partial correlations between ROIs, disinhibition, and EF were computed after controlling for total intracranial volume, Mini-Mental State Examination, diagnosis, age, and education. Brain regions significantly correlated with disinhibition (ACC, OFC, IFG, and temporal lobes) and EF (MFG) were entered into separate hierarchical regressions to determine which brain regions predicted disinhibition and EF. OFC was the only brain region to significantly predict disinhibition, and MFG significantly predicted EF performance. A multivariate general linear model demonstrated a significant interaction between ROIs and cognitive-behavioral functions.
  
  
  CONCLUSIONS
  These results support a specific association between orbitofrontal areas and behavioral management as compared with dorsolateral areas and EF.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA. casey.krueger@baylorhealth.edu
authors.forename: Casey E
authors.initials: CE
authors.lastname: Krueger
authors.forename: Victor
authors.initials: V
authors.lastname: Laluz
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.forename: John M
authors.initials: JM
authors.lastname: Neuhaus
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
mesh_terms: D000342:Affective Symptoms / Q000175:diagnosis / Q000209:etiology*; D000368:Aged; D000704:Analysis of Variance; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000523:psychology; D003704:Dementia / Q000150:complications / Q000473:pathology / Q000523:psychology; D056344:Executive Function / Q000502:physiology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D012919:Social Behavior